Oncotarget

Research Papers: Gerotarget (Focus on Aging):

Epigallocatechin-3-gallate induces oxidative phosphorylation by activating cytochrome c oxidase in human cultured neurons and astrocytes

Gloria Castellano-González, Nicolas Pichaud, J. William O. Ballard, Alban Bessede, Helder Marcal and Gilles J. Guillemin _

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Oncotarget. 2016; 7:7426-7440. https://doi.org/10.18632/oncotarget.6863

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Abstract

Gloria Castellano-González1, Nicolas Pichaud2, J. William O. Ballard3, Alban Bessede4, Helder Marcal5 and Gilles J. Guillemin1

1 MND and Neurodegenerative Diseases Research Group, Australian School of Advanced Medicine (ASAM), Macquarie University, Sydney, Australia

2 Department of Biological and Environmental Sciences, University of Gothenburg, Göteborg, Sweden

3 School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, Australia

4 Immusmol Pty Ltd, Pessac, France

5 Topical Therapeutics Research Group, School of Medical Sciences, The University of New South Wales, Sydney, Australia

Correspondence to:

Gilles J. Guillemin, email:

Keywords: epigallocatechin-3-gallate, ATP, neurodegeneration, cytochrome c oxidase, mitochondria, Gerotarget

Received: October 27, 2015 Accepted: December 24, 2015 Published: January 09, 2016

Abstract

Mitochondrial dysfunction and resulting energy impairment have been identified as features of many neurodegenerative diseases. Whether this energy impairment is the cause of the disease or the consequence of preceding impairment(s) is still under discussion, however a recovery of cellular bioenergetics would plausibly prevent or improve the pathology. In this study, we screened different natural molecules for their ability to increase intracellular adenine triphosphate purine (ATP). Among them, epigallocatechin-3-gallate (EGCG), a polyphenol from green tea, presented the most striking results. We found that it increases ATP production in both human cultured astrocytes and neurons with different kinetic parameters and without toxicity.

Specifically, we showed that oxidative phosphorylation in human cultured astrocytes and neurons increased at the level of the routine respiration on the cells pre-treated with the natural molecule. Furthermore, EGCG-induced ATP production was only blocked by sodium azide (NaN3) and oligomycin, inhibitors of cytochrome c oxidase (CcO; complex IV) and ATP synthase (complex V) respectively. These findings suggest that the EGCG modulates CcO activity, as confirmed by its enzymatic activity. CcO is known to be regulated differently in neurons and astrocytes. Accordingly, EGCG treatment is acting differently on the kinetic parameters of the two cell types. To our knowledge, this is the first study showing that EGCG promotes CcO activity in human cultured neurons and astrocytes. Considering that CcO dysfunction has been reported in patients having neurodegenerative diseases such as Alzheimer’s disease (AD), we therefore suggest that EGCG could restore mitochondrial function and prevent subsequent loss of synaptic function.


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